Synergistic and residual pesticidal compositions containing plant essential oils

ABSTRACT

Synergistic and residual pesticidal compositions containing synergistic and residual mixtures of plant essential oils and/or their constituents, plant essential oils and/or their constituents in admixture with known active pesticidal compounds or plant essential oils and/or their constituents in admixture with other compounds not previously used as active ingredients in pesticidal formulations, such as, for example, so called signal transduction modulators. In addition, the present invention is directed to a method for controlling pests by applying a pesticidally effective amount of the above synergistic and residual pesticidal compositions to a locus where pest control is desired.

This application is related to U.S. Provisional Patent Application Ser.No. 60/094,463, filed Jul. 28, 1998, U.S. Provisional Patent ApplicationSer. No. 60/100,613, filed Sep. 16, 1998, and U.S. Provisional PatentApplication Ser. No. 60/122,803, filed Mar. 3, 1999, the entiredisclosures of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates, in general, to pesticidal compositionsand, in particular, synergistic and residual pesticidal compositionscontaining plant essential oils and/or their constituents. In oneaspect, the present invention relates to synergistic pesticidalcompositions containing synergistic mixtures of plant essential oilsand/or their constituents. In another aspect, the present inventionrelates to synergistic pesticidal compositions containing certain plantessential oils and/or their constituents in admixture with known activepesticidal compounds. In another aspect, the present invention relatesto residual pesticidal compositions containing certain plant essentialoils and/or their constituents in admixture with known active pesticidalcompounds and other compounds not previously used as active ingredientsin pesticidal compositions, such as, for example, so called signaltransduction modulators known to have beneficial use in thepharmaceutical arts. In a further aspect, the present invention relatesto a method for controlling pests by the application of pesticidallyeffective amounts of the above synergistic and residual pesticidalcompositions to a locus where pest control is desired.

BACKGROUND OF THE INVENTION

Pests (invertebrates, insects, arachnids, mites, larvae thereof, etc.)are annoying to humans for a myriad of reasons. They have annually costhumans billions of dollars in crop losses and in the expense of keepingthem under control. For example, the losses caused by pests inagricultural environments include decreased crop yield, reduced cropquality, and increased harvesting costs.

Over the years, synthetic chemical pesticides have provided an effectivemeans of pest control. For example, one prior approach involves the useof complex, organic insecticides, such as those disclosed in U.S. Pat.Nos. 4,376,784 and 4,308,279. Other prior approaches employ absorbentorganic polymers for widespread dehydration of the insects. See, U.S.Pat. Nos. 4,985,251; 4,983,390; 4,818,534; and 4,983,389. Use ofinorganic salts as components of pesticides has also been tried, asdisclosed in U.S. Pat. Nos. 2,423,284 and 4,948,013, European PatentApplication No. 462 347, Chemical Abstracts 119(5):43357q (1993) andFarm Chemicals Handbook, page c102 (1987).

However, it has become increasingly apparent that the widespread use ofsynthetic chemical pesticides has caused detrimental environmentaleffects that are harmful to humans and other animals. For instance, thepublic has become concerned about the amount of residual chemicals thatpersist in food, ground water and the environment, and that are toxic,carcinogenic or otherwise incompatible to humans, domestic animalsand/or fish. Moreover, some target pests have even shown an ability todevelop resistance to many commonly used synthetic chemical pesticides.In recent times, regulatory guidelines have encouraged the developmentof potentially less harmful pesticidal compositions via stringentrestrictions on the use of certain synthetic pesticides. As a result,elimination of effective pesticides from the market has limitedeconomical and effective options for controlling pests. As analternative, botanical pesticides are of great interest because they arenatural pesticides, i.e., toxicants derived from plants that are safe tohumans and the environment. Historically, botanical pesticides, such astobacco, pyrethrum, derris, hellebore, quassia, camphor and turpentine,have long been used. Of the botanical pesticides, pyrethrum (also knownas caucasian pyrethrum, dalmatic pyrethrum, pesticide chrysanthemum,natural pyrethrum and pyrethrin) has found widespread use.

Pyrethrum, which is extracted from the flowers of a chrysanthemum grownin Kenya and Ecuador, acts on insects with phenomenal speed causingimmediate paralysis, while at effective pesticidal concentrationsexhibits negligible toxic effects on humans and warm-blooded animals.Use of pyrethrins for industrial or agricultural applications, however,is attendant with several disadvantages. For example, they requirefrequent treatments because they readily decompose when exposed todirect sunlight. Pyrethrins are also neurotoxic to cold-blooded animals,such as fishes, reptiles, etc. Moreover, the supply of pyrethrins islimited and substantial processing is required to bring the naturalproduct to market, and large-scale production is very expensive. Unlesspyrethrins are formulated with a synergist, most initially paralyzedinsects recover to once again become pests.

Synergists are compounds that, although typically possessing no directtoxic effect at the dosage employed, are able to substantially enhancethe observed toxicity of a pesticide with which they are combined.Synergists are found in most household, livestock and pet aerosols toenhance the action of the fast knockdown pesticides, e.g., pyrethrum,allethrin, and resmethrin, against flying insects. Synergists arerequired in pesticidal formulations containing pyrethrum, for example,because target insects produce an enzyme (cytochrome P-450) that attackspyrethrum and breaks it down, thereby making it effective in knocking aninsect down, but ineffective for killing in many cases. As such, thesesynergists act by inhibiting P-450-dependent polysubstrate monooxygenaseenzymes (PSMOs) produced by microsomes, which are subcellular unitsfound in the liver of mammals and in some insect tissues that degradepyrethrum and other pesticidal compounds, such as pyrethrum, allethrin,resmethrin, and the like.

Piperonyl butoxide (PBO) is the main pesticide synergist in commerce.PBO, however, is a synthetic product that has recently been scrutinizedby regulatory agencies and certain other groups. As a result, theindustry has turned to synthetic pyrethroids, which are very photostablein sunlight and are generally effective against most agricultural insectpests. Pyrethroids are not as safe as pyrethrins, however, anddisadvantageously persist in the environment for longer periods.Further, many insects disadvantageously develop resistance topyrethroids.

Many natural products used as insecticides, including plant essentialoils, do not provide adequate control of pests in that they are not verystable and break down quickly, thereby failing to provide toxic residualproperties. Products such as pyrethrum, although highly toxic to pestson contact when used properly in pesticidal formulations, are noteffective pesticides for many applications because they lack residualproperties, thereby increasing the frequency and cost of pesticideapplications, as well as increased risk and exposure to the environment.

Accordingly, there is a great need for novel synergistic and residualpesticidal compositions containing no level or substantially lowerlevels of synthetic pyrethroids, chlorinated hydrocarbons,organophosphates, carbamates and the like. In addition, there is a needfor methods for using same that address the problems described above,i.e. are safe to humans and the environment and relatively inexpensiveto use in obtaining acceptable levels of insect or pest control.

SUMMARY OF THE INVENTION

A primary object of the present invention is to provide novel pesticidalcompositions that contain at least one plant essential oil, derivativesthereof, and/or their constituents as a synergist and at least one knownconventional pesticidal compound.

Another object of the present invention is to provide pesticidalcompositions containing synergistic mixtures or blends of plantessential oils and/or their constituents.

Still another object of the present invention is to provide new uses forsignal transduction modulators in pesticidal compositions comprising atleast one plant essential oil, derivatives thereof and/or theirconstituents, and/or conventional pesticides.

A further object of the present invention is to provide pesticidalcompositions wherein the active synergistic compositions of the presentinvention can be employed in a reduced amount and still achieve thedesired pest control.

A further object of the present invention is to provide novel, residualpesticidal compositions that contain admixtures of certain compounds,natural or synthetic, with certain plant essential oils and/or theirconstituents that act to residualize the toxic effects of pesticidalcompositions containing the plant essential oils and/or theirconstituents.

A still further object of the present invention is to provide a methodfor controlling pest growth by the application of the compositions ofthe present invention to a locus where such control is desired.

Another object of the present invention is to provide a pesticidalcomposition and method for mechanically and neurally controlling pests,e.g., invertebrates, insects, arachnids, larvae thereof, etc.

A further object of the present invention is to provide a safe,non-toxic pesticidal composition and method that will not harm theenvironment.

Another object of the present invention is to provide a pesticidalcomposition and method that has a pleasant scent and that can be appliedwithout burdensome safety precautions.

Still another object to of the present invention is to provide apesticidal composition and method as described above which can beinexpensively produced or employed.

Yet another object of the present invention is to provide a pesticidalcomposition and method to which pests cannot build resistance.

The above and other objects are accomplished by the present inventionwhich is directed to (1) a synergistic and residual pesticidalcomposition containing at least two plant essential oil, derivativesthereof, and/or their constituents, (2) synergistic and residualpesticidal compositions comprising plant essential oils and/or theirconstituents in admixture with known active pesticidal compounds, (3)synergistic and residual pesticidal compositions comprising plantessential oils and/or their constituents in admixture with compounds notpreviously used as active ingredients in pesticidal compounds, e.g.,signal transduction modulators (inhibitors and/or activators), or (4)synergistic and residual pesticidal compositions comprising known activepesticidal compounds in admixture with other compounds not previouslyused as active ingredients in pesticidal compounds, e.g., signaltransduction modulators. It will be understood that throughout thisdescription, the meaning of term “signal transduction modulators” shallencompass inhibitors and/or activators. In addition, the presentinvention is directed to methods for controlling pests by the applying apesticidally effective amount of the above synergistic and residualpesticidal compositions to a locus where pest control is desired.

Additional objects and attendant advantages of the present inventionwill be set forth, in part, in the description that follows, or may belearned from practicing or using the present invention. The objects andadvantages may be realized and attained by means of theinstrumentalities and combinations particularly recited in the appendedclaims. It is to be understood that the foregoing general descriptionand the following detailed description are exemplary and explanatoryonly and are not to be viewed as being restrictive of the invention, asclaimed.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

All patents, patent applications and literatures cited in thisdescription are incorporated herein by reference in their entirety. Inthe case of inconsistencies, the present disclosure, includingdefinitions, will prevail.

In one embodiment, the present invention provides a synergistic andresidual pesticidal composition comprising, in admixture with a suitablecarrier and optionally with a suitable surface active agent, at leasttwo plant essential oil compounds or derivatives thereof, includingracemic mixtures, enantiomers, diastereomers, hydrates, salts, solvates,metabolites, analogs, homologs, etc.

Each plant essential oil or derivative thereof, which may be extractedfrom natural sources or synthetically made, generally contains, as amajor constituent, an acyclic monoterpene alcohol or aldehyde, abenzenoid aromatic compound containing at least one oxygenatedsubstituent or side chain, or a monocarbocyclic terpene generally havinga six membered ring bearing one or more oxygenated substituents.Examples of such essential oils or their constituents include, but arenot limited to, members selected from the group consisting of aldehydeC16 (pure), alpha-terpineol, amyl cinnamic aldehyde, amyl salicylate,anisic aldehyde, benzyl alcohol, benzyl acetate, cinnamaldehyde,cinnamic alcohol, carvacrol, carveol, citral, citronellal, citronellol,dimethyl salicylate, eucalyptol (cineole), eugenol, iso-eugenol,galaxolide, geraniol, guaiacol, ionone, d-limonene, menthol, methylanthranilate, methyl ionone, methyl salicylate, alpha-phellandrene,pennyroyal oil, perillaldehyde, 1- or 2-phenyl ethyl alcohol, 1- or2-phenyl ethyl propionate, piperonal, piperonyl acetate, piperonylalcohol, D-pulegone, terpinen-4-ol, terpinyl acetate, 4-tertbutylcyclohexyl acetate, thyme oil (white and red), thymol,trans-anethole, vanillin, ethyl vanillin, and the like. As these plantessential oil compounds are known and used for other uses, they may beroutinely prepared by a skilled artisan by employing known methods.

Further, the present invention provides new uses for so called signaltransduction modulators. Signal transduction modulators have been knownto show therapeutic utility or potential in the pharmaceutical arts, buthave heretofore not been known to exhibit utility in the pesticidalarts. As such, the synergistic and residual pesticidal compositions ofthe present invention may comprise known active pesticidal compoundsand/or at least one of the above plant essential oil compounds, and atleast one signal transduction modulator. Preferred signal transductionmodulators include those that are effective for the disruption of cyclicadenosine monophosphate (cAMP)/cAMP-dependent protein kinase, tyrosinekinase, MEK 1 or MEK 2, calcium phospholipid-dependent protein kinase(PKC), mitogen activated protein kinase family members,calcium-calmodulin-dependent protein kinase, growth factor receptor,octopamine receptor, etc. Preferred signal transduction modulatorsinclude, but are not limited to, forskolin, PD98059 (also known as2-(2-amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran or2′-amino-3′-methoxy-flavone), geldanamycin, lavendustin A, lavendustinB, lavendustin C, genistein, herbimycin A,2-hydroxy-5-(2,5-di-hydroxybenzyl)amino-benzoic acid, methyl2,5-dihydroxycinnamate, tyrphostin, staurosporine, cytochalasin B, andthe like.

In another preferred embodiment, the present invention includes asynergistic pesticidal composition for agricultural use comprising amixture of eugenol, alpha-terpineol, citronellal, thymol andtrans-anethole. Data below shows that trans-anethole synergizes theaction of thyme oil and thyme oil derivatives such as thymol andcarvacrol, which are believed to antagonize mitochondrial electrontransport pathways in pests.

In another preferred embodiment, the present invention is directed to asynergistic pesticidal composition for controlling household pestscomprising alpha-terpineol, benzyl alcohol, 2-phenylethyl alcohol and/or2-phenylethyl propionate. Data below shows that this embodiment ishighly effective, i.e., exhibited increased toxicity, against fire antsand cockroaches compared to the individual plant essential oils, alone.

In still another preferred embodiment, the present invention is directedto synergistic and residual pesticidal compositions comprising at leastone plant essential oil compound and at least one pesticidal agentselected from the group consisting of a natural insecticide compound,chlorinated hydrocarbon, an organophosphate, a carbamate and the like,in admixture with a suitable carrier and optionally a suitable surfaceactive agent. Preferred pesticidal agents include, without limitation,allethrin, azadirachtin (neem), carbaryl, chlorpyrifos, DDT,fenvalorate, malathion, permethrin, pyrethrum, resmethrin, rotenone,pyrethroids, etc.

In a further preferred embodiment, the present invention encompassessynergistic and residual pesticidal compositions comprising at least oneof the above plant essential. oil compounds and one or more membersselected from the group consisting of pyrethrolone, allethrolone,chrysanthemic acid, chrysanthemyl alcohol, cis-jasmone, and dimethylsulfoxide (DMSO), in admixture with a suitable carrier and optionally asuitable surface active agent.

In another preferred embodiment, the present invention is directed to asynergistic and residual pesticidal composition comprising at least oneof the above plant essential oil compounds, a pesticidal agent and asignal tranduction modulator.

It will be appreciated by the skilled artisan that the synergistic andresidual pesticidal compositions of the present invention unexpectedlyexhibit excellent pesticidal activities at sub-lethal dosage regimens,i.e., using active pesticidal agents at lesser concentrations than theindividual compounds. Further, it will be appreciated by the skilledartisan that the synergistic and residual pesticidal compositions of thepresent invention unexpectedly exhibit pesticidal activity for extendedperiods of time, (i.e. using natural compounds as residual insecticidesthat in and of themselves provide little, if any, residual pesticideproperties). Without wishing to be bound by the following theories, itis possible that plant essential oils antagonize a pest's nervereceptors or may act as P-450 inhibitors. Alternatively, plant essentialoils may act via an alternative mode of action. In the case wherepyrethrum is the pesticidal agent in admixture with one or more plantessential oils, it is believed that pyrethrum facilitates penetration ofa pest cuticle, thereby increasing access of the plant essential oils tothe pest's nerve receptors. Further, another possibility is thatpyrethrum and other pesticidal agents biochemically synergize the plantessential oils. The pesticidal agents may also disrupt energy levelswithin the insect's metabolism, thereby synergizing the antagonisticaction of so-called octopamine affectors. In any event, the net effectof the increased toxicity and synergized action of the inventivesynergistic composition disclosed herein is heretofore unknown andunexpected.

Use of synergistic and residual pesticidal compositions of the presentinvention generally results in 100% mortality on contact and provideresidual toxic properties for at least two weeks. As such, they areadvantageously employed as pesticidal agents in uses such as, withoutlimitation, agriculture, organic farming, households, professional pestcontrol, pet bedding, foliage application, underwater or submergedapplication, solid treatment, soil incorporation application, seedlingbox treatment, stalk injection and planting treatment, ornamentals, andagainst termites, mosquitoes, fire ants, head lice, dust mites, etc.

With respect to plants, the synergistic and residual pesticidalcompositions resist weathering which includes wash-off caused by rain,decomposition by ultra-violet light, oxidation, or hydrolysis in thepresence of moisture or, at least such decomposition, oxidation andhydrolysis as would materially decrease the desirable pesticidalcharacteristic of the synergistic and residual compositions or impartundesirable characteristics to the synergistic and residualcompositions. The synergistic and residual compositions are sochemically inert that they are compatible with substantially any otherconstituents of the spray schedule, and they may be used in the soil,upon the seeds, or the roots of plants without injuring either the seedsor roots of plants. They may also be used in combination with otherpesticidally active compounds.

The term “carrier” as used herein means a material, which may beinorganic or organic and of synthetic or natural origin, with which theactive compound is mixed or formulated to facilitate its application tothe plant, seed, soil or other object to be treated, or its storage,transport and/or handling. In general, any material that may becustomarily employed as a carrier in insecticidal, herbicidal, orfungicidal formulations, are suitable for use with the presentinvention. The inventive synergistic and residual pesticidalcompositions of the present invention may be employed alone or in theform of mixtures with such solid and/or liquid dispersible carriervehicles and/or other known compatible active agents, especially plantprotection agents, such as other insecticides, acaricides, miticides,nematocides, fungicides, bactericides, rodenticides, herbicides,fertilizers, growth-regulating agents, etc., if desired, or in the formof particular dosage preparations for specific application madetherefrom, such as solutions, emulsions, suspensions, powders, pastes,and granules which are thus ready for use. The synergistic and residualpesticidal compositions of the present invention can be formulated ormixed with, if desired, conventional inert (i.e. plant compatible orherbicidally inert) pesticide diluents or extenders of the type usablein conventional pesticide formulations or compositions, e.g.conventional pesticide dispersible carrier vehicles such as gases,solutions, emulsions, suspensions, emulsifiable concentrates, spraypowders, pastes, soluble powders, dusting agents, granules, foams,pastes, tablets, aerosols, natural and synthetic materials impregnatedwith active compounds, microcapsules, coating compositions for use onseeds, and formulations used with burning equipment, such as fumigatingcartridges, fumigating cans and fumigating coils, as well as ULV coldmist and warm mist formulations, etc.

Formulations containing the synergistic and residual compositions of thepresent invention may be prepared in any known manner, for instance byextending the synergistic and residual compositions with conventionalpesticide dispersible liquid carriers and/or dispersible solid carriersoptionally with the use of carrier vehicle assistants, e.g. conventionalpesticide surface-active agents, including emulsifying agents and/ordispersing agents, whereby, for example, in the case where water is usedas diluent, organic solvents may be added as auxiliary solvents.Suitable liquid diluents or carriers include water, petroleumdistillates, or other liquid carriers with or without surface activeagents. The choice of dispersing and emulsifying agents and the amountemployed is dictated by the nature of the composition and the ability ofthe agent to facilitate the dispersion of the synergistic and residualcompositions of the present invention. Generally, it is desirable to useas little of the agent as is possible, consistent with the desireddispersion of the synergistic and residual compositions of the presentinvention in the spray so that rain, dew, fog, etc. does not re-emulsifythe synergistic and residual compositions of the present invention afterit is applied to the plant and wash it off the plant. Non-ionic,anionic, amphoteric, or cationic dispersing and emulsifying agents maybe employed, for example, the condensation products of alkylene oxideswith phenol and organic acids, alkyl aryl sulfonates, complex etheralcohols, quaternary ammonium compounds, and the like.

Liquid concentrates may be prepared by dissolving a composition of thepresent invention with a non-phytotoxic solvent and dispersing thesynergistic and residual compositions of the present inventions in waterwith suitable surface active emulsifying and dispersing agents. Examplesof conventional carrier vehicles for this purpose include, but are notlimited to, aerosol propellants which are gaseous at normal temperaturesand pressures, such as Freon; inert dispersible liquid diluent carriers,including inert organic solvents, such as aromatic hydrocarbons, e.g.benzene, toluene, xylene, alkyl naphthalenes, etc., halogenatedespecially chlorinated, aromatic hydrocarbons, e.g. chloro-benzenes,etc., cycloalkanes, e.g. cyclohexane, etc., paraffins, e.g. petroleum ormineral oil fractions, chlorinated aliphatic hydrocarbons, e.g.methylene chloride, chloroethylenes, etc., alcohols, e.g. methanol,ethanol, propanol, butanol, glycol, etc., as well as ethers and estersthereof, e.g. glycol monomethyl ether, etc., amines, e.g. ethanolamine,etc., amides, e.g. dimethyl formamide etc., sulfoxides, e.g. dimethylsulfoxide, etc., acetonitrile, ketones, e.g. acetone, methyl ethylketone, methyl isobutyl ketone, cyclohexanone, etc., and/or water, aswell as inert dispersible finely divided solid carriers such as groundnatural minerals, e.g. kaolins, clays, vermiculite, alumina, silica,chalk, i.e. calcium carbonate, talc, attapulgite, montmorillonite,kieselguhr, etc., and ground synthetic minerals, e.g. highly dispersedsilicic acid, silicates, e.g. alkali silicates, etc.

Surface-active agents, i.e., conventional carrier vehicle assistants,that may be employed with the present invention include, withoutlimitation, emulsifying agents, such as non-ionic and/or anionicemulsifying agents, e.g. sodium dodecyl benzene sulfonate, polyethyleneoxide esters of fatty acids, polyethylene oxide ethers of fattyalcohols, alkyl sulfates, alkyl sulfonates, aryl sulfonates, albuminhydrolyzates, etc. and especially alkyl arylpolyglycol ethers, magnesiumstearate, sodium oleate, etc.

In accordance with the principles of the present invention, insecticidescan also be prepared as either water or oil based suspensions. Knownquantities of the active materials can be dispersed into water or oilusing high speed agitation as delivered from machines such as colloidmills, waring blenders, high speed homogenizers or lightening mixers.These systems are capable of imparting a large amount of energy into theliquid resulting in the generation of very small drops of one liquiddispersed throughout the other. If water is the continuous phase, it isa water-based suspension. If the continuous phase is oil, it is an oilbased suspension. To aid in the dispersion of the one fluid intoanother, emulsifiers and dispersants may be added. These agents can benon-ionic and/or anionic emulsifying agents (e.g. polyethylene oxideesters of fatty acids, polyethylene oxide ethers of fatty alcohols,alkyl sulfates, alkyl sulfonates, aryl sulfonates, albumin hydrolyzates,etc. and especially alkyl arylpolyglycol ethers). To stabilize themixture, to prevent the agglomeration of the droplets over time, theviscosity of the liquid is adjusted using agents such as xantham gums,polyacryamides or polyacrylates, and swelling clays such as attapulgite,bentonite or veegum. The preferred particle size of the suspendedparticles is the 3 to 5 micron range. Concentrations of the active mayrange from 0.01 to 70% with the typical concentration approximately 1 to50% w/w.

In the preparation of wettable powders, dust or granulated formulations,the active ingredient is dispersed in and on an appropriately dividedcarrier. In the formulation of the wettable powders the aforementioneddispersing agents as well as lignosulfonates can be included. Dusts areadmixtures of the compositions with finely divided solids such as talc,amorphous or fumed silica, attapulgite clay, kaolin, kieselguhr,pyrophyllite, chalk, diatomaceous earths, vermiculite, calciumphosphates, calcium and magnesium carbonates, sulfur, flours, and otherorganic and inorganic solids which acts carriers for the pesticide.These finely divided solids preferably have an average particle size ofless than about 50 microns. A typical dust formulation useful forcontrolling insects contains 1 part of synergistic and residualcomposition and 99 parts of diatomaceous earth or vermiculite. Granulesmay comprise porous or nonporous particles. The granule particles arerelatively large, a diameter of about 400-2500 microns typically. Theparticles are either impregnated or coated with the inventive pesticidalcompositions from solution. Granules generally contain 0.05-15%,preferably 0.5-5%, active ingredient as the pesticidally-effectiveamount. Thus, the contemplated are formulations with solid carriers ordiluents such as bentonite, fullers earth, ground natural minerals, suchas kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite ordiatomaceous earth, vermiculite, and ground synthetic minerals, such ashighly-dispersed silicic acid, alumina and silicates, crushed andfractionated natural rocks such as calcite, marble, pumice, sepioliteand dolomite, as well as synthetic granules of inorganic and organicmeals, and granules of organic materials such as peanut shell, paperwaste, sawdust, coconut shells, corn cobs and tobacco stalks. Adhesives,such as carboxymethyl cellulose, natural and synthetic polymers, (suchas gum arabic, polyvinyl alcohol and polyvinyl acetate), and the like,may also be used in the formulations in the form of powders, granules oremulsifiable concentrations.

If desired, colorants such as inorganic pigments, for example, ironoxide, titanium oxide and Prussian Blue, and organic dyestuffs, such asalizarin dyestuffs, azo dyestuffs or metal phthalocyanine dyestuffs, andtrace elements, such as salts of iron, manganese, boron, copper, cobalt,molybdenum and zinc may be used.

If desired, volatile organic compounds suitable as the fragranceingredient for use in formulations for household or pet applications,include, but are not limited to, amyl salicylate, citronellol,citronelloxyacetaldehyde, cyclamen aldehyde, citronellyl isobutyrate,coumarin, cyclohexyl acetate, cyclohexyl butyrate, diethyl malonate,ethyl 2-acetyl-5-ketohexanoate, isobornyl acetate, linalool, phenethylalcohol, undecanol, alpha-hexylcinnamaldehyde, 2-methylhexanol, hexalon,phenylacetaldehyde, cis-3-hexen-1-ol, cyclamal, veronol, eugenol, Lyral,Galaxolide, Citralva, musk ambrette, terpinyl acetate, geraniol,alpha-damascone, alpha-methylionone, and the like. Illustrative ofvolatile essential oils are oil of Bergamot, cedar leaf, cedar wood,geranium, lavender, white cedar, sandalwood oil, rose extract, violetextract, galbanum oil, and the like. Synthetic types of organicfragrances are described in publications such as U.S. Pat. Nos.4,314,915; 4,411,829; and 4,434,366.

In commercial or agricultural applications, the present inventionencompasses carrier composition mixtures in which the synergistic andresidual compositions are present in an amount substantially betweenabout 6.01-95% by weight, and preferably 0.5-90% by weight, of themixture, whereas carrier composition mixtures suitable for directapplication or field application generally contemplate those in whichthe active compound is present in an amount substantially between about0.0001-10%, preferably 0.01-1%, by weight of the mixture. Thus, thepresent invention contemplates over-all formulations that comprisemixtures of a conventional dispersible carrier vehicle such as (1) adispersible inert finely divided carrier solid, and/or (2) a dispersiblecarrier liquid such as an inert organic solvent and/or water, preferablyincluding a surface-active effective amount of a carrier vehicleassistant, e.g. a surface-active agent, such as an emulsifying agentand/or a dispersing agent, and an amount of the active compound which iseffective for the purpose in question and which is generally betweenabout 0.0001-95%, and preferably 0.01-95%, by weight of the mixture.

The synergistic and residual compositions can also be used in accordancewith so-called ultra-low-volume process, i.e. by applying such compoundsor by applying a liquid composition containing the same, via veryeffective atomizing equipment, in finely divided form, e.g. averageparticle diameter of from 50-100 microns, or even less, i.e. mist form,for example by airplane crop spraying techniques. Only up to at mostabout a few liters/hectare are needed. In this process it is possible touse highly concentrated liquid compositions with said liquid carriervehicles containing from about 20 to 95% by weight of the synergisticand residual compositions or even the 100% active substances alone, e.g.about 20-100% by weight of the synergistic and residual compositions.The mixture of active materials may be applied, without limitation, insufficient amounts so as to provide about 0.2 to 2 and preferably about0.5 to 1.5 pounds of active materials per acre. Moreover, the requiredamount of the synergistic and residual composition contemplated hereinmay be applied per acre treated in from 1 to 200 gallons or more ofliquid carrier and/or diluent or in from about 5 to 500 pounds of inertsolid carrier and/or diluent. The concentration in the liquidconcentrate will usually vary from about 10 to 95% by weight and in thesolid formulations from about 0.5 to 90% by weight. Satisfactory sprays,dusts, or granules for general use contain from about ¼ to 15 pounds ofactive synergistic and residual compositions per acre.

Furthermore, the present invention encompasses methods for killing,combating or controlling pests, which comprises applying to at least oneof correspondingly (a) such pests and (b) the corresponding habitatthereof, i.e. the locus to be protected, e.g. to a growing crop, to anarea where a crop is to be grown or to a domestic animal, acorrespondingly combative, a pesticidally effective amount, or toxicamount of the particular synergistic and residual compositions of theinvention alone or together with a carrier as noted above. The instantformulations or compositions may be applied in any suitable usualmanner, for instance by spraying, atomizing, vaporizing, scattering,dusting, watering, squirting, sprinkling, pouring, fumigating, and thelike. The method for controlling insects comprises applying theinventive composition, ordinarily in a formulation of one of theaforementioned types, to a locus or area to be protected from theinsects, such as the foliage and/or the fruit of plants. The compound,of course, is applied in an amount sufficient to effect the desiredaction. This dosage is dependent upon many factors, including thetargeted pest, the carrier employed, the method and conditions of theapplication, whether the formulation is present at the locus in the formof an aerosol, or as a film, or as discrete particles, the thickness offilm or size of particles, and the like. Proper consideration andresolution of these factors to provide the necessary dosage of theactive compound at the locus to be protected are within the skill ofthose versed in the art. In general, however, the effective dosage ofthe compound of this invention at the locus to be protected—i.e., thedosage with which the pest comes in contact—is of the order of 0.001 to0.5% based on the total weight of the formulation being applied, thoughunder some circumstances the effective concentration will be as littleas 0.0001% or as much as 20%, on the same basis.

The synergistic and residual pesticidal compositions and methods of thepresent invention are effective against a wide variety of pests and itwill be understood that the pests exemplified and evaluated in theworking Examples herein is representative of such a wider variety. Forinstance, the present invention can be used to control pests that attackplants or warm-blooded animals, stored products and fabrics.Representative crop plants that can be so treated include, withoutlimitation, cotton, corn, deciduous and citrus fruits, tomatoes, maize,ornamental plants, potatoes, rice, soybean, sugar beets, tobacco, wheat,etc. Representative animals that can be protected or treated by thepresent invention include, without limitation, humans, horses, dogs,cats, cattle, sheep, goats, hogs, etc. Representative stored productsthat can be protected from pest attack by the present invention include,without limitation, grains, flour and flour products, tobacco andtobacco products, processed foods and the like. Representative fabricsthat can be protected from pest attack by the invention are wool,cotton, silk, linen and the like.

The composition and method of the present invention will be furtherillustrated in the following, non-limiting Examples. The Examples areillustrative of various embodiments only and do not limit the claimedinvention regarding the materials, conditions, weight ratios, processparameters and the like recited herein.

EXAMPLE 1 Synergistic Effect of Plant Essential Oils and/or theirConstituents with Pyrethrum on the American Cockroach

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Ten cockroaches were used for each cross-walktreatment. Each individual component, with the exception of pyrethrum,was used at 100 mg/jar. In the co-treatment experiment withoutpyrethrum, each chemical was used at 20 mg/jar. In the cotreatmentexperiment with pyrethrum (25% pure pyrethrins), each plant essentialoil was used at 20 mg/jar. Pyrethrum was used at 2 mg/jar. Results areshown below. % Mortality Treatment 24 hrs. 48 hrs. 72 hrs. Control 0 0 01 − phenylethyl alcohol (100 mg) 0 0 10 2 − α-Terpineol (100 mg) 20 3060 3 − benzyl alcohol (100 mg) 0 20 40 4 − phenylethyl propionate (100mg) 100 5 − eugenol (100 mg) 100 6 − pyrethrum (55% pure) (2 mg/jar) 0 010 1 + 2 + 3 (20 mg each) 40 70 80 1 + 2 + 3 + 4 (20 mg each) 60 100 1 +2 + 3 + 4 + 5 (20 mg each) 100 1 + pyrethrum (20 mg + 2 mg) 0 20 20 2 +pyrethrum (20 mg + 2 mg) 40 60 100 3 + pyrethrum (20 mg + 2 mg) 20 40 804 + pyrethrum (20 mg + 2 mg) 100 5 + pyrethrum (20 mg + 2 mg) 100

EXAMPLE 2 Synergistic Effects of Plant Essential Oils and/or theirConstituents with Pyrethrum on the American Cockroach

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 3times. In the cotreatment experiment with pyrethrum, ten mg/jar of plantessential oils and/or their constituents were used. Pyrethrum was usedat one mg/jar in all tests. Results are shown below. Treatment %Mortality at 24 hrs. Control 0 1 − Thymol (20 mg/jar) 0 2 − Thyme Oil(20 mg/jar) 0 3 − Blend 5 (20 mg/jar) 0 4 − Eugenol (20 mg/jar) 0 5 −Pyrethrum (1 mg/jar) 0 1 (10 mg/jar) + pyrethrum 50 2 (10 mg/jar) +pyrethrum 70 3 (10 mg/jar) + pyrethrum 80 4 (10 mg/jar) + pyrethrum 100

The tested dose of Thyme oil, Thymol and Blend 5 did not induce anydeath or sign of toxicity (body weight and appetite) against female rats(8-10 week-old rat) up to 5 days after treatment. The Blend-5 is acombination of plant essential oils consisting of thymol, eugenol,trans-anethole, alpha-terpineol, and citronellal.

Examples 1 and 2. These Examples show synergistic activity of asynergistic composition containing plant essential oils and/or theirconstituents and pyrethrum (25% pure pyrethrins) at lesserconcentrations, i.e., each at sub lethal dosages.

EXAMPLE 3 Synergistic and Residual Effects of Mixture of Plant EssentialOil(s) with Pyrethrum and Pyrethrum Derivatives against AmericanCockroach

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. The averaged results are shown below. % Mortality at timeinterval in days after treatment Treatment 1 hr. 3 5 7 10 20 30 45 60Control 0 0 0 0 0 0 0 0 0 Thymol (30 mg/jar) 30 10 0 C-Alcohol (3mg/jar) + C-Acid (3 mg/jar) 0 0 0 Pyrethrum (45% pure) (.3 mg/jar) 0 0 0Thymol (30 mg) + Pyrethrum (.3 mg) 100 100 100 100 100 100 100 80 100Thymol + C-Alcohol + C-Acid 100 100 100 100 100 80 80 80 70 (30 mg) + (3mg) + (3 mg) 4-Blend (25 mg) (phenethyl alcohol, phenethyl 40 40 10 0propionate, benzyl alcohol, α-terpineol) 4-Blend (25 mg) + pyrethrum (.3mg) 100 100 100 100 80 80 60 40 0The data above demonstrate the synergistic and residual effects of oneor more plant essential oils with pyrethrum. The increased toxicity andincreased residual action of the synergistic blends are unexpected andprovide distinct benefits over existing pesticide technologies.

EXAMPLE 4 Synergistic and Residual Effects of Thymol with Pyrethrum

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 3 10 30 45 Control 0 0 0 0 0 Thymol (30mg/jar) 30 10 0 Thymol (10 mg/jar) 10 0 0 Thymol (5 mg/jar) 0 0 0Pyrethrum (25% pure) (1 mg/jar) 10 10 0 Pyrethrum (25% pure) (0.3mg/jar) 0 0 Pyrethrum (25% pure) (0.1 mg/jar) 0 0 Thymol (30 mg) +Pyrethrum (1 mg) 100 100 100 100 80 Thymol (30 mg) + Pyrethrum (0.3 mg)100 100 100 100 80 Thymol (30 mg) + Pyrethrum (0.1 mg) 100 100 100 10050 Thymol (10 mg) + Pyrethrum (1 mg) 100 100 100 100 50 Thymol (10 mg) +Pyrethrum (0.3 mg) 100 100 100 100 50 Thymol (10 mg) + Pyrethrum (0.1mg) 100 100 100 100 20 Thymol (5 mg) + Pyrethrum (1 mg) 100 100 100 10010 Thymol (5 mg) + Pyrethrum (0.3 mg) 100 100 100 90 0 Thymol (5 mg) +Pyrethrum (0.1 mg) 100 100 70 40 0

These data demonstrate the definite synergy and increased residualtoxicity of thymol and sublethal amounts of pyrethrum. This synergy andincreased residual action at such low levels is unexpected andsignificant.

EXAMPLE 5 Synergistic and Residual Effect of Mixture of Plant EssentialOil Constituents with Pyrethrins and DMSO

A sample of pyrethrins in an acetone solution at a ratio of 1 partpyrethrins to 100 parts acetone was prepared. A second sample containingfour plant essential oil constituents (alpha-terpineol, benzyl alcohol,phenyl ethyl alcohol and phenyl ethyl propionate) in equal proportionsby weight was prepared. Then, the first and second samples were combinedin a 1:1 ratio to obtain a synergized 4-blend composition, 1 part 4-15blend to 0.01 parts pyrethrins. The synergized 4-blend composition wasthen applied to uncovered 9 cm glass petri dishes at 100 ul each. Thesecond sample was applied to uncovered 9 cm glass petri dishes at 500 uleach. After exposure for one hour, allowing the acetone to evaporate,ten fire ants were placed in each petri dish and observed to determinethe time to accomplish LD 90, which is the lethal dose required to kill90% of the test population.

It was observed that the 100 ul of synergized 4-blend killed three timesfaster than the 500 ul of 4-blend alone. The 100 ul of synergized4-blend killed the ants in one minute and fifty seconds whereas the 500ul of 4-blend alone killed the ants in four minutes and forty-fiveseconds. The ants exposed to the 4-blend composition exhibited increasedsigns of neurotoxic effect, including tremors and lack of coordination.This data shows that the level of the insecticidal plant essential oilsin the synergistic compositions of the present invention may bedecreased to lower levels of active ingredient in suitable end-useformulations from 5% to 1%, adding 0.01% pyrethrins, to achieve a fasterknockdown and kill, at less cost. Moreover, the synergized samplecontinued to provide faster residual knockdown and mortality againstfire ants than the unsynergized sample for at least fourteen (14) daysafter exposure. Similar experiments were conducted using dimethylsulfoxide (DMSO) and it also proved to be synergistic with plantessential oils and the synergized sample also provided residual toxicproperties.

EXAMPLE 6 Synergistic and Residual Effects of Thymol with PyrethrumDerivatives

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 3 10 30 Control 0 0 0 0 Thymol (30mg/jar) 50 0 0 Chrysanthemate Ester (0.3 mg/jar) 0 0 0 ChrysanthemateEster (0.6 mg/jar) 0 0 0 Chrysanthemate Ester (3.0 mg/jar) 20 0 0 Thymol(30 mg) + Chrysanthemate Ester 0 0 (0.3 mg) 100:1 Thymol (30 mg) +Chrysanthemate Ester 0 0 (0.6 mg) 50:1 Thymol (30 mg) + ChrysanthemateEster 100 100 100 100 (3.0 mg) 10:1

These data demonstrate the definite synergy and increased residualtoxicity of thymol and sublethal amounts of pyrethrum derivatives. Thissynergy and increased residual action at such low levels is unexpectedand significant.

EXAMPLE 7 Synergistic and Residual Effects of Mixture of Thymol withPyrethrum Derivatives and Signal Transduction Modulators againstAmerican Cockroach

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 3 5 10 30 45 60 Control 0 0 0 0 0 0 0Thymol (20 mg/jar) 10 10 0 Cis-Jasmone (3 mg/jar) 0 0 0 PD 98059 (40ug/jar) 0 0 0 Lavandustin A 0 0 0 (40 ug/jar) Thymol + Cis-Jasmone 100100 100 100 100 100 70 Thymol + PD 98059 100 100 100 100 100 100 60Thymol + Lavandustin A 100 100 100 80 100 100 40The data above demonstrate the synergistic and residual effects ofthymol with pyrethrum derivative Cis-Jasmone and signal transductionmodulators such as PD 98059 and Lavandustin A. The increased toxicityand increased residual action of the synergistic blends are unexpectedand provide distinct benefits over existing pesticide technologies. Thisdata also demonstrates the ratios necessary to produce residual toxiceffects.

EXAMPLE 8 Synergistic and Residual Effects of Benzyl Alcohol withPyrethrum and Other Synergists

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 7 30 45 Control 0 0 0 0 Benzyl Alcohol(B-A) (100 mg/jar) 80 0 0 B-A (50 mg/jar) 0 0 0 B-A (50 mg/jar) + Thymol(1 mg) 100 0 B-A (50 mg/jar) + Thymol (5 mg) 100 0 B-A (50 mg/jar) +Pyrethrum (25% pure) 100 100 60 0 (1 mg) B-A (50 mg/jar) + Pyrethrum(25% pure) 100 100 100 30 (5 mg) B-A (50 mg/jar) + Cis-Jasmone (1 mg)100 0 0 B-A (50 mg/jar) + Chrysanthemyl Alcohol 100 0 0 (1 mg) B-A (50mg/jar) + Chrysanthemic Acid (1 mg) 100 0 0

EXAMPLE 9 Synergistic and Residual Effects of Benzyl Alcohol withChrysanthemates

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 7 14 21 Control 0 0 0 Benzyl Alcohol(B-A) (100 mg/jar) 70 0 Chrysanthemate Ester (C-Ester) (1 mg/jar) 0 0B-A (100 mg/jar) + C-Ester (1 mg) 100 30 0 Chrysanthemyl Alcohol(C-Alcohol) (1 mg) + 0 0 0 Chrysanthemic Acid (C-Acid) (1 mg) B-A (100mg/jar) + C-Alcohol (1 mg) + C-Acid 100 50 0 (1 mg) C-Ester (10 mg/jar)30 0 B-A (100 mg/jar) + C-Ester (10 mg) 100 100 0 C-Alcohol (10mg/jar) + C-Acid (10 mg/jar) 40 0 B-A (100 mg) + C-Alcohol (10 mg) +C-Acid 100 100 (10 mg)

These data demonstrate the definite synergy and increased residualtoxicity of benzyl alcohol with synergists. This synergy and increasedresidual action at such low levels is unexpected and significant. Thisdata also demonstrates the ratios necessary to produce residual toxiceffects.

EXAMPLE 10 Synergistic and Residual Effects of Benzyl Alcohol withSynergists

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 7 14 21 30 45 Control 0 0 Benzyl Alcohol(B-A) (100 mg/jar) 70 0 Pulegone (10 ug/jar) 30 20 Eugenol (10 ug/jar)10 20 Cis-Jasmone (10 mg/jar) 0 0 Tetrahydrofurfuryl Alcohol (THFA) 0 0(10 mg/jar) Thymol (15 mg/jar) 30 0 B-A (100 mg/jar) + Pulegone (10 ug)100 100 0 B-A (100 mg/jar) + Eugenol (10 ug) 100 100 20 0 B-A (100mg/jar) + Cis-Jasmone 100 100 50 50 40 0 (10 mg) B-A (100 mg/jar) + THFA(10 mg) 100 100 40 50 20 0 B-A (100 mg/jar) + Thymol (15 mg) 100 100 5020 0 0

These data demonstrate the definite synergy and increased residualtoxicity of benzyl alcohol with synergists. This synergy and increasedresidual action at such low levels is unexpected and significant. Thisdata also demonstrates the ratios necessary to produce residual toxiceffects.

EXAMPLE 11 Synergistic and Residual Effects of Benzyl Alcohol withSignal Transduction Modulators

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 7 14 21 Control 0 0 0 Benzyl Alcohol(B-A) (100 mg/jar) 100 0 0 B-A (100 mg/jar) + Lavandustin A (40 ug) 100100 0 B-A (100 mg/jar) + PD 98059 (40 ug) 100 100 0 B-A (100 mg/jar) +Forskolin (40 ug) 100 100 20 B-A (100 mg/jar) + Geldanamycin (100 ng)100 80 0

These data demonstrate the increased residual toxicity of benzyl alcoholwith signal transduction modulators. This synergy and increased residualaction at such low levels is unexpected and significant. This data alsodemonstrates the ratios necessary to produce residual toxic effects.

EXAMPLE 12 Synergistic Effects of Thymol with Conventional Insecticides

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 7 14 21 Control 0 Thymol (10 mg/jar) 0Malathion (75 ug/jar) 0 Deltamethrin (5 ug/jar) 30 Permethrin (5 ug/jar)0 Thymol (10 mg/jar) + Malathion (75 ug/jar) 0 Thymol (10 mg/jar) +Deltamethrin (5 ug/jar) 100 Thymol (10 mg/jar) + Permethrin (5 ug/jar) 0

These data demonstrate the synergy of thymol with deltamethrin even atvery low levels. This synergy is unexpected and significant.

EXAMPLE 13 Synergistic and Residual Effects of Thymol with Carbaryl

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 7 14 21 30 Control 0 Thymol (15 mg/jar)20 0 Carbaryl (1.0 mg/jar) 90 20 0 Carbaryl (0.1 mg/jar) 30 0 Thymol (15mg/jar) + Carbaryl 100 100 100 100 0 (1.0 mg/jar) Thymol (15 mg/jar) +Carbaryl 100 80 10 0 (0.1 mg/jar)

These data demonstrate the synergy and residual toxicity of thymol withcarbaryl even at very low levels. This synergy and residual toxicity isunexpected and significant.

EXAMPLE 14 Synergistic and Residual Effects of Thymol with ConventionalInsecticides

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and the cockroacheswere exposed to the jars. Five cockroaches were used for each cross-walktreatment, with two replicates/treatment. This experiment was repeated 2times. Results are shown below. % Mortality at time interval in daysafter treatment Treatment 1 hr. 7 14 21 30 45 Control 0 Thymol (15mg/jar) 10 20 10 Malathion (100 ug/jar) 100 90 60 Deltamethrin (5ug/jar) 30 0 0 Permethrin (10 ug/jar) 10 0 0 Thymol (15 mg/jar) +Malathion 40 0 0 (100 ug/jar) Thymol (15 mg/jar) + Deltamethrin 100 7080 100 70 50 (5 ug/jar) Thymol (15 mg/jar) + Permethrin 80 100 90 50 300 (10 ug/jar)

These data demonstrate the synergy and residual toxicity of thymol withdeltamethrin and permethrin at very low levels. This synergy andresidual toxicity is unexpected and significant. Thymol and malathionare antagonistic.

EXAMPLE 15 Synergistic Effect of Plant Essential Oils and/or theirConstituents and Pyrethrum on the American Cockroach

This experiment was performed to determine whether pyrethrum (25% purepyrethrins) act as a synergist to the plant essential oils and/or theirconstituents or vice versa. Five cockroaches were used for eachcross-walk treatment, with two replicates/treatment. This experiment wasrepeated 2 times. Results are shown below. Treatment % Mortality at 24hrs. Control 0 1 − Thymol (50 mg/jar) 20 2 − Thyme Oil (35 mg/jar) 30 3− Blend 5 (40 mg/jar) 30 4 − pyrethrum (1 mg/jar) 0 1 + pyrethrum 70 2 +pyrethrum 90 3 + pyrethrum 100The dose of pyrethrum which did not induce any lethal effects on Am.Cockroaches was mixed as 1 part relative to the test concentration ofplant essential oils and/or their constituents. Without wishing to bebound by the following theory, it appears that pyrethrum acts as asynergist to the plant essential oils and their constituents tested.None of the test doses induced any toxicity against female rats.

EXAMPLE 16 Synergistic Toxicity among Plant Essential Oil Constituents

Several experiments were performed to exemplify that binary mixtures ofplant essential oil compounds act synergistically. Early 5^(th) instarlarvae of Spodoptera litura (15-20 mg) were treated topically on thedorsum with doses of pure compounds as per standard protocols. Treatedlarvae were placed on diet in 5 cm plastic petri dishes and mortalityobserved at 24 hours post-treatment. For each treatment there were fourreplicates with 10 larvae each. Results are shown below. Treatments(μg/larva) Mortality (%) Experiment 1 Acetone control 0 Thymol (35) 25Citronellal (35) 0 Thymol (35) + citronellal (35) ND Experiment 2Acetone control 0 Thymol (40) 27.5 Thymol (40) + citronellal (40) 67.5Experiment 3 Acetone control 0 Thymol (40) 25 Thymol (40) + citronellal(40) 57.5 Experiment 4 Acetone control 0 Thymol (40) 80 Thymol (40) +citronellal (40) 93.3 Experiment 5 Acetone control 0 Thymol (40) 20Thymol (40) + citronellal (40) 77.5 Experiment 6 Thymol (35) 32.5α-terpineol (35) 5 Both at 35 32.5 Experiment 7 Thymol (35) 60 Eugenol(35) 0 Both at 35 50 Experiment 8 Eugenol (90) 27.5 α-terpineol (90) 20Both at 90 35 Experiment 9 Citronellal (110) 10 α-terpineol (110) 15Both at 110 65 Experiment 10 Citronellal (110) 12.5 Eugenol (110) 20Both at 110 40 Experiment 11 Thymol (35) 37.5 t-anethole (35) 12.5 Bothat 35 100 Experiment 12 Thymol (40) 40 t-anethole (40) 12.5 Thymol(40) + t-anethole (25) 97.5 Thymol (40) + t-anethole (20) 90 Thymol(40) + t-anethole (15) 87.5 Thymol (40) + t-anethole (10) 80 Thymol(40) + t-anethole (5) 70 Thymol (40) + t-anethole (2.2) 55 Experiment 13t-anethole (60) 17.5 α-terpineol (60) 7.5 Both at 60 97.5 Experiment 14t-anethole (60) 30 Eugenol (60) 8 Both at 60 95 Experiment 15 t-anethole(70) 24 Citronellal (70) 6 Both at 70 40

Experiments 2-5 show that thymol is synergized by citronellal whenapplied in equal doses. Experiments 6-10 show that that thymol is notsynergized by α-terpineol or eugenol. Eugenol does not appear to besynergized by α-terpineol or citronellal. However, α-terpineol andcitronellal look to act synergistically (exp. 9). Experiments 11 & 12show that trans-anethole is a potent synergist for thymol, even at aratio of 1:8. Experiments 13-15 show that trans-anethole is an effectivesynergist for eugenol, α-terpineol and citronellal.

EXAMPLE 17 Synergistic Effect of Plant Essential Oils and Propargiteagainst Two-Spotted Spider Mites

Mixtures of 5-Blend (thymol, trans-anethole, α-terpineol, eugenol, andcitronellal) with and without the commercial miticide, propargite(Omite™) were tested against adult mites on bean leaf discs. Treatmentsconsisted of spraying adult mites (direct toxicity) and observing fortoxicity versus survival. For each treatment there were 5 replicateswith 10 mites in each. Mortality was determined. Results are shownbelow. % Survival at: Treatment 24 hrs. 48 hrs. 72 hrs. Control 4% 5%32% 5-Blend, 0.5% 0% 0% 0% Omite, 0.01% 5% 5% 22% 5-Blend + Omite 30%48% 52%

Conclusions: When sprayed directly on adult mites, neither 5-Blend norOmite are toxic up to 72 hours. However, the combination of the twoproducts shows enhanced toxicity. These data are unexpected and provideadvantages over existing pesticide technologies.

EXAMPLE 18 Synergistic Effect of Plant Essential Oils with ConventionalInsecticides against Spodoptera litura

Mixtures of 5-Blend (thymol, trans-anethole, α-terpineol, eugenol, andcitronellal) with conventional insecticides were tested against 5-dayold larvae of Spodoptera litura (2^(nd) instar) on cabbage leaf piecesdipped in test solution. Mortality was observed at 24 and 48 hours. Foreach treatment there were 5 replicates with 50 larvae per replicate(n=250). Results are shown below. Mortality (%) Treatment 24 hrs. 48hrs. Control 0 0 5-Blend(1% = 1:100 dilution) 2 6 Tebufenozide(Confirm ™), 0.1 ppm 4.5 41 Cypermethrin (Cymbush ™), 0.01 ppm 78 805-Blend + Tebufenozide 39 74 5-Blend + Cypermethrin 58 89

Conclusions: In this experiment, 5-Blend synergized tebufenozide at 24hours and 48 hours. The results with cypermethrin are inconclusive dueto initial toxicity. These data are unexpected and provide advantagesover existing pesticide technologies.

EXAMPLE 19 Synergistic Effect of Plant Essential Oils withChrysanthemates against Spodoptera litura

Mixtures of 5-Blend (thymol, trans-anethole, α-terpineol, eugenol, andcitronellal) and potential synergists were tested by application tocabbage leaf discs dipped in 1% emulsions. There were 4 leaf discs pertreatment. Ten 3-day old (2^(nd) instar) Spodoptera litura larvae perdisc. Potential synergists and insecticides were dissolved in THFA/Tween20 (carrier/emulsifier) at 10% active ingredient level; mixed with5-Blend at 1:10 ratio of synergist to 5-Blend. Mortality was observed at24 and 48 hours. For each treatment there were 5 replicates with 50larvae per replicate (n=250). Results are shown below. Mortality (%)Treatment 24 hrs. 48 hrs. Control (THFA/Tween 20) 0 0 Cis-Jasmone 0 0Chrysanthemic Acid 0 0 Chrysanthemyl Alcohol 0 0 Chrysanthemic Esters 55 5-Blend 20 30 5-Blend + Cis-Jasmone 60 85 5-Blend + Chrysanthemic Acid72.5 87.5 5-Blend + Chrysanthemyl Alcohol 70 87.5 5-Blend +Chrysanthemic Esters 60 75

Conclusions: In this experiment, at a ratio of 10:1, 5-Blend issynergized by cis-jasmone, and the chrysanthemates. There was virtuallyno damage to the leaf discs in the synergized 5-Blend treatments, 30%damage in the 5-blend alone, and more than 80% in the remainingtreatments. The control was completely consumed within 48 hours. Thesedata are unexpected and provide advantages over existing pesticidetechnologies.

EXAMPLE 20 Synergistic Effect of Benzyl Alcohol with Pyrethrum againstSpodoptera litura

Mixtures of 5-Blend and potential synergists were tested by applicationto cabbage leaf discs dipped in 1% emulsions. There were 4 leaf discsper treatment; ten 3-day old (2^(nd) instar) Spodoptera litura larvaeper disc. Potential synergists and insecticides were dissolved inTHFA/Tween 20 at 10% a.i.; mixed with 5-Blend at 1:10 ratio(synergist:5-Blend). In this example, THFA/Tween 20 at a ratio of 6:1was used as a carrier/emulsifier for pyrethrum (20% pure pyrethrins) andother test substances. The sample size for each treatment is 40 (4replicates with 10 insects each) of Spodoptera litura. Results are shownbelow. Mortality (%) Treatment 24 hrs. Control (THFA/Tween 20) 10Pyrethrum 40:1 (ingredient ratio) 37.5 Pyrethrum 20:1 40 Pyrethrum 10:1100 Benzyl Alcohol 15 Benzyl Alcohol + Pyrethrum 40:1 72.5 BenzylAlcohol + Pyrethrum 20:1 82.5 Benzyl Alcohol + Pyrethrum 10:1 100

Conclusions: Benzyl alcohol appears to synergize pyrethrum, at least atthe lower levels of active ingredient. The effect is obscured at thehighest rate because there was 100% mortality with pyrethrum alone.These data are unexpected and provide advantages over existing pesticidetechnologies.

EXAMPLE 21 Synergistic and Residual Effects of Plant Essential Oils withConventional Insecticides and Synergists, and Signal TransductionModulators

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and Americancockroaches were exposed to the jars. Five cockroaches were used foreach cross-walk treatment, with two replicates/treatment. Thisexperiment was repeated 2 times. Results are shown below. % Mortality attime interval in days after treatment Treatment 1 hr. 7 14 21 30 Control0 Benzyl Alcohol (100 mg) 100 0 0 Mixture ES-2a: 100 100 100 BenzylAlcohol (B-A) (100 mg) Tetrahydrofurfuryl Alcohol (THFA) (10 mg) PD98059 (100 ug) Trans-Anethole (10 mg) Pyrethrum (55% pure pyrethrins) (3mg) Mixture ES-2b: 100 100 0 B-A (100 mg) THFA (10 mg) PD 98059 (100 ug)Trans-Anethole (10 mg) Chrysanthemate Ester (5 mg)

These data demonstrate the synergistic and residual toxic effects ofplant essential oils with pyrethrum and signal transduction modulatorsat very low levels. This synergy and residual toxicity is unexpected andsignificant. Signal transduction modulators may also synergizeconventional pesticides and chrysanthemates as it does here withpyrethrum and chrysanthemate ester.

EXAMPLE 22 Synergistic and Residual Effects of Benzyl Alcohol withTrans-Anethole

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and Americancockroaches were exposed to the jars. Five cockroaches were used foreach cross-walk treatment, with two replicates/treatment. Thisexperiment was repeated 2 times. Results are shown below. % Mortality attime interval in days after treatment Treatment 1 hr. 7 14 21 30 Control0 Benzyl Alcohol (100 mg/jar) 70 0 Trans-Anethole (10 mg/jar) 0 BenzylAlcohol (B-A) (100 mg/jar) with: Trans-Anethole 10 mg/jar (1:10) 100 10080 40 0 Trans-Anethole 2 mg/jar (1:50) 100 0 Trans-Anethole 1 mg/jar(1:100) 100 0 Mixture ES-2b: 100 100 0 B-A (100 mg) THFA (10 mg) PD98059 (100 ug) Trans-Anethole (10 mg) Chrysanthemate Ester (5 mg)

These data demonstrate the synergistic and residual toxic effects ofplant essential oils with pyrethrum and signal transduction modulatorsat very low levels. This synergy and residual toxicity is unexpected andsignificant. Signal transduction modulators may also synergizeconventional pesticides and chrysanthemates as it does here withpyrethrum and chrysanthemate ester.

EXAMPLE 23 Synergistic and Residual Effects of Thymol with Pyrethrum andSignal Transduction Modulators

Glass jars were treated with different concentrations of test chemicalsin acetone. The acetone was allowed to evaporate and Americancockroaches were exposed to the jars. Five cockroaches were used foreach cross-walk treatment, with two replicates/treatment. Thisexperiment was repeated 2 times. Results are shown below. % Mortality attime interval in days fter treatment Treatment 1 hr. 7 14 21 30 45 60Control 0 Mixture ES-A: (100 mg thymol + 40 ug PD98059) 15 minute briefexposure 100 0 0 24 hour continuous exposure 100 100 100 60 0 MixtureES-B: (100 mg thymol + 3 mg pyrethrum) (Pyrethrum = 55% pure pyrethrins)15 minute brief exposure 100 100 100 85 85 65 65 24 continuous exposure100 100 100 100 85 70 80 Mixture ES-C: (100 mg thymol + 20 mg PhenethylPropionate + 3 mg Cis-Jasmone) 15 minute brief exposure 100 0 24 hourcontinuous exposure 100 100 0After ten minutes of exposure, all roaches from all three products areuncontrolled and unable to walk on the wall of the jars. These datademonstrate the synergistic and residual toxic effects of thymol withother plant essential oils in admixture with pyrethrum and signaltransduction modulators at very low levels. This synergy and residualtoxicity is unexpected and significant.

EXAMPLE 24 Synergistic Effect of Phenethyl Propionate with PlantEssential Oils and Thymol

In this bioassay, aqueous emulsions (1:400 a.i. to water) of thymol or5-blend (thymol, trans-anethole, eugenol, α-terpineol, and citronellal)were applied, with and without phenethyl propionate (PEP), to cabbageleaf discs and 3^(rd) instar larvae of Spodoptera litura were exposed tothe treated discs after drying. There were five replicates with 10larvae per replicate, and this was repeated two times. Mortality wasobserved after 24 hours exposure. Results are shown below. Mortality (%)Treatment 24 hrs. Control 1 5-Blend 73 PEP 8 5-Blend + PEP (1:1) 84Thymol 98 PEP 2 Thymol + PEP (1:1) 84

Conclusions: Phenethyl propionate appears to synergize thymol and the5-Blend. PEP can be used as a diluent for thymol and 5-Blend withoutappreciable loss of activity. These data are unexpected and provideadvantages over existing pesticide technologies.

As can be seen from the above discussion, the synergistic and residualcombinations of active compounds according to the present invention aremarkedly superior to known pesticidal agents/active compoundsconventionally used for pest control in the household and inagricultural areas. The pesticidal effectiveness of the particular newsynergistic and residual combinations of active compounds of the presentinvention is substantially (and surprisingly) higher than the sum of theseparate effects of the individual active compounds.

Although illustrative embodiments of the invention have been describedin detail, it is to be understood that the present invention is notlimited to those precise embodiments, and that various changes andmodifications can be effected therein by one skilled in the art withoutdeparting from the scope and spirit of the invention as defined by theappended claims.

1-15. (canceled)
 16. A pesticidal composition, comprising apesticidally-acceptable carrier and a pesticidally-effective amount of apesticidally-active agent comprising pyrethrum and menthol.
 17. Thepesticidal composition of claim 16, wherein the active agent interfereswith neurotransmission in invertebrates.
 18. The pesticidal compositionof claim 17, wherein the active agent interferes with octopaminereceptor sites in invertebrates.
 19. A pesticidal composition,comprising a pesticidally-acceptable carrier and apesticidally-effective amount of a pesticidally-active agent consistingessentially of pyrethrum and menthol.
 20. A pesticidal composition,comprising a pesticidally-acceptable carrier and apesticidally-effective amount of a pesticidally-active agent consistingof pyrethrum and menthol.